Melphalan and Palifermin in Treating Patients Undergoing An Autologous Peripheral Stem Cell Transplant for Stage II or III Multiple Myeloma

April 14, 2014 updated by: Muneer Abidi, Barbara Ann Karmanos Cancer Institute

Phase I Dose Escalation Trial of High Dose Melphalan Conditioning Regimen With Palifermin for Cytoprotection Followed by Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Keratinocyte growth factors, such as palifermin, may help prevent symptoms of mucositis, or mouth sores, in patients receiving melphalan before a peripheral stem cell transplant for multiple myeloma.

PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given together with palifermin in treating patients undergoing an autologous peripheral stem cell transplant for stage II or stage III multiple myeloma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of high-dose melphalan when administered with palifermin in patients undergoing autologous peripheral blood stem cell transplantation for stage II or III multiple myeloma.

Secondary

  • Assess overall response (complete and partial response and stable disease) in these patients at 28 and 100 days post-transplantation.
  • Assess the efficacy of palifermin as a cytoprotective agent in reducing incidence and duration of mucositis in patients treated with this regimen.
  • Assess patient-reported outcomes and impact of palifermin on quality of life of these patients.
  • Assess the qualitative and quantitative toxicities of this regimen in these patients.

OUTLINE: This is a dose-escalation study of melphalan. Patients are stratified according to creatinine clearance (normal vs < 60 mL/min).

Patients receive high-dose melphalan IV on day -2 and palifermin IV on days -5 to -3 and 1-3. Patients undergo autologous peripheral blood stem cell transplantation on day 0.

In each stratum, cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients complete questionnaires about overall health, mouth and throat soreness (MTS), and activity limitations due to MTS once daily on days -5 to 28.

After completion of study treatment, patients are followed at days 28 and 100 and then periodically thereafter.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma

    • Stage II or III disease
  • Must have undergone successful stem cell mobilization (≥ 2.0 x 10^6 CD34+ cells/kg)
  • No oral lesions from any other etiology
  • No unhealed mucositis from induction treatment

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Amylase and lipase normal
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • Creatinine normal (stratum 1 only)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No history of allergic reaction attributed to melphalan

  • No uncontrolled illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
  • No psychiatric illness or social situation that would preclude study compliance
  • No hepatitis B or C positivity
  • No prior or concurrent pancreatitis
  • No known sensitivity to any of the study drugs, including E. coli-derived products

PRIOR CONCURRENT THERAPY:

  • Prior bone marrow or stem cell transplantation allowed
  • No prior palifermin
  • More than 30 days since prior investigational agents
  • No concurrent dialysis
  • No concurrent amifostine
  • No concurrent prophylactic oral cryotherapy during melphalan administration

  • No concurrent mouthwash solutions containing any of the following:

    • Chlorhexidine
    • Hydrogen peroxide
    • Diphenhydramine hydrochloride
  • No concurrent recombinant interleukin-11 or sargramostim (GM-CSF)

  • No concurrent sucralfate in suspension form

    • Sucralfate tablets allowed
  • No concurrent povidone-iodine rinses
  • No concurrent glutamine as a prophylactic agent for mucositis
  • No other concurrent investigational agents
  • No concurrent antithymocyte globulin suppression or alemtuzumab
  • No concurrent rituximab

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Palifermin & Melphalen

Palifermin 60 mcg/kg/d of the actual body weight unless actual body weight is >40% of the Ideal body weight (IBW), then adjusted body weight (AdBW) will be used for dose calculations - administered on Day - 5,-4, - 3 and then repeated on Day +1, +2 and +3

Dose of Melphalan + Palifermin (Normal Renal Function): All given on Day -2:

Dose Level 1- 200 mg/m2 I.V; Dose Level 2- 220 mg/m2 I.V; Dose Level 3- 240 mg/m2 I.V; Dose Level 4- 260 mg/m2 I.V; Dose Level 5- 280 mg/m2 I.V;

Dose of Melphalan + Palifermin (Renal Dysfunction CrCl. <60)adm. via I.V.:

Dose Level 1- 140 mg/m2; Dose Level 2- 160 mg/m2; Dose Level 3- 180 mg/m2; Dose Level 4- 200 mg/m2; Dose Level 5- 220 mg/m2;
Biological: Palifermin
Palifermin 60 mcg/kg/d of the actual body weight unless actual body weight is >40% of the Ideal body weight (IBW), then adjusted body weight (AdBW) will be used for dose calculations - administered on Day - 5,-4, - 3 and then repeated on Day +1, +2 and +3
Other Names:
  • Kepivance
Drug: melphalan

Dose of Melphalan + Palifermin (Normal Renal Function): All given on Day -2:

Dose Level 1- 200 mg/m2 I.V; Dose Level 2- 220 mg/m2 I.V; Dose Level 3- 240 mg/m2 I.V; Dose Level 4- 260 mg/m2 I.V; Dose Level 5- 280 mg/m2 I.V;

Dose of Melphalan + Palifermin (Renal Dysfunction CrCl. <60)adm. via I.V.:

Dose Level 1- 140 mg/m2; Dose Level 2- 160 mg/m2; Dose Level 3- 180 mg/m2; Dose Level 4- 200 mg/m2; Dose Level 5- 220 mg/m2;

Other Names:
  • Alkeran
Other: questionnaire administration
Day -5 to Day +28
Procedure: autologous peripheral blood stem cell transplantation
Day 0
Other: quality-of-life assessment
Day -5 to Day +28

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of melphalan when treated with palifermin to prevent mucositis
Time Frame: Days -5, -4, -3, 2, +1, +2 and +3
Days -5, -4, -3, 2, +1, +2 and +3

Secondary Outcome Measures

Outcome Measure
Time Frame
Dose-limiting toxicity
Time Frame: Days -5, -4, -3, 2, +1, +2 and +3
Days -5, -4, -3, 2, +1, +2 and +3
Evaluate the efficacy of Palifermin as a cytoprotective agent in reducing incidence and duration of Grade 3 and 4 mucositis due to high dose Melphlan
Time Frame: Day -5 to Day +28
Day -5 to Day +28
Overall response
Time Frame: At Day 28 and Day100 after autologous transplant when treated with combination of palifermin and Melphalan
At Day 28 and Day100 after autologous transplant when treated with combination of palifermin and Melphalan
Reduction in incidence and duration of mucositis
Time Frame: Days -5 to Day +28
Days -5 to Day +28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Muneer H. Abidi, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

October 1, 2011

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

June 4, 2007

First Submitted That Met QC Criteria

June 4, 2007

First Posted (Estimate)

June 5, 2007

Study Record Updates

Last Update Posted (Estimate)

April 15, 2014

Last Update Submitted That Met QC Criteria

April 14, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000547155
  • P30CA022453 (U.S. NIH Grant/Contract)
  • WSU-2006-119

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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